Objective: The long range goal of this program is to determine the effect(s) of aging on the ability of mouse liver to regulate the expression of a specific gene -- albumin. Experiments are designed to determine the relative rate of albumin synthesis and secretion in young, mature and aged mouse liver by radioimmunoassay. The steady state level of albumin mRNA will be determined by cDNA-mRNA hybridization kinetics (Rot curve analysis). The objective of these experiments is to determine whether age-associated changes in albumin synthesis occur and whether this is reflected in changes in ablumin mRNA levels. In addition, the effect of aging on the steady-state level of albumin synthesizing polysomes will be determined using the 125I-labeled anti-albumin binding assay. Studies will also be done to determine whether there is an age-associated effect on the distribution and/or the integrity of albumin synthesizing polysomes. In these experiments we will determine whether there is an increase of non-membrane bound polysomes (albumin) and/or an increase in the albumin mRNP pool. In order to facilitate these studies, cDNA and genomic clones of mouse albumin DNA sequences will be prepared. These clones will also be used to determine the effect of age on albumin mRNA turnover. Albumin synthesis and mRNA levels are modulated by glucocorticoids (hydrocortisone and hexamethasone) and by analogs of cAMP (Bt2cAMP and 8-BrcAMP). The ability of aged mouse liver to respond after treatment with these factors will be determined. The major objective in this study is to determine if the regulatory events involved in the modulation of albumin synthesis and mRNA levels can function efficiently in aged liver cells.